Hair loss is of concern to a large number of men and women. In many individuals, hair loss (i.e., alopecia) causes embarrassment, and/or psychological problems such as depression. Although alopecia is more common in men (e.g., male pattern baldness or androgenic alopecia) than women (e.g., female pattern baldness), it is a significant concern to both men and women. Indeed, millions of dollars and countless hours of research have been dedicated to solving this problem.
The mature hair follicle is a complex mini-organ that has a tightly regulated growth cycle. During postnatal development, the follicle undergoes successive phases of active hair shaft production (anagen), apoptosis-driven regression (catagen), and a quiescent phase (telogen) (Paus et al., New Engl. J. Med., 341:491-497, 1999). During the anagen phase, active hair growth involves cell proliferation in the proximal follicular epithelium, followed by invasion of the elongating follicle into the subcutaneous tissue, differentiation of the epithelium at the base of the follicle, and formation of hair matrix cells, which proliferate and generate a new hair shaft. When the proliferation capacity of the matrix cells is exhausted, a regression phase (catagen) of the hair growth cycle ensues, through which the lower part of the follicle undergoes programmed cell death and involution (Costsarelis et al., Am. J. Pathol., 151:1505-1509, 1997). At this point the follicle enters telogen, the resting period. The cycle is then repeated.
Scalp hair follicles cycle independently of each other. On average, of 100,000 scalp hairs, approximately 90% are in the anagenic (i.e., growth) phase, while the remaining 10% are in the telogenic (i.e., resting) phase, at any given point in time (Whiting, “Disorders of Hair,” In: Scientific American Medicine, ed. by Dale and Federman, New York:Web MD Scientific American Medicine, 1999, pages 2:XIII:1-7). The anagen phase lasts an average of about three years, with a range of one to seven years, while the telogen phase lasts an average of about three months, after which the resting hairs are shed and new hairs grow in. The average rate of scalp hair growth is approximately 0.35 mm/day (i.e., approximately 1 inch every 2-3 months). In the anagenic phase, the cells surrounding the dermal papilla actively divide approximately every 12 hours, in order to produce cells which line up, grow longer, and begin to keratinize. During a transition stage (i.e., the catagenic or regression phase) that occurs between the anagen and telogen phases, mitosis no longer occurs and the bulb detaches itself from the papilla and rises towards the surface. In the telogenic phase, the hair is fully keratinized and is ready to be expelled. After three to four months, another mitotic cycle begins in the germination zone of the hair and another hair follicle is formed.
An average loss of 100 scalp hairs/day is considered to be normal, with a higher number being shed on days when the hair is washed. In diagnosing hair disorders, it is important to determine whether the shedding is abnormal and whether shed hairs break off or come out by the roots. Hair normally comes out by the roots. However, trauma or excessive fragility of the hair may cause it to break. In examination of patients, hair pull tests may indicate abnormal shedding. In this test, groups of 10-20 hairs are grasped between the index finger and thumb and pulled steadily. Extraction of more than 20% of the grasped hairs potentially indicates abnormal shedding, usually involving telogen hairs. Telogen hairs (“club hairs”) are easily recognized, due to their whitish club-shaped bulbs and lack of root sheaths. Normally, anagen hairs are difficult to detach and have blackish, indented roots with intact root sheaths (Whiting, “Disorders of Hair,” In: Scientific American Medicine, ed. by Dale and Federman, New York:Web MD Scientific American Medicine, 1999, pages 2:XIII:1-7).
There are various forms of alopecia observed in humans. The most common is androgenetic alopecia, although diffuse alopecia, telogen effluvium, anagen effluvium (i.e., anagen arrest), alopecia areata, traumatic alopecia, trichotillomania, cicatricial alopecia, and other types of hair loss are also observed. In addition, hair loss associated with cancer treatment is quite common and of great concern to a large number of patients. Indeed, treatment with various drugs (e.g., alpha blockers, angiotensin converting enzyme inhibitors, anticoagulants, anticonvulsants, antithyroids, beta blockers, calcium channel blockers, cholesterol reducers, H2 receptor blockers, non-steroidal anti-inflammatories, retinoids, retinol, tricyclic antidepressants, and others) can result in hair loss for a significant number of patients. Nutritional deficiencies or excesses also can cause hair loss.
Depending upon the severity, treatment and management of alopecia ranges from continuing observation to medical and surgical treatment, to use of a hairpiece or wig. Minoxidil has been approved by the U.S. Food and Drug Administration for topical use in both men and women. The therapeutic effect of minoxidil is variable: Two percent topical minoxidil produces visible hair growth in approximately ⅓ of male and female androgenetic patients, fine hair growth in approximately ⅓ of patients, and no hair growth in approximately ⅓ of patients. In addition, if the drug is effective, use of the medication must be continued indefinitely; otherwise, loss of hairs that were gained during therapy may occur (Scow et al., Am. Fam. Physician, 59:21892194, 1999). Side effects of minoxidil administration include scalp irritation and increased facial hair. The mechanism of action by which minoxidil produces hair growth is not fully understood.
Other compounds that have found use in treatment of alopecia include orally administered finasteride. At a dosage of 1 mg/day given for 2 years to male patients between 18 and 41 years of age, visible hair growth was observed in 66% of cases and further hair loss was prevented in 83% (Whiting, “Disorders of Hair,” In: Scientific American Medicine, ed. by Dale and Federman, New York:Web MD Scientific American Medicine, 1999, pages 2:XIII:1-7). However, a similar treatment regimen in post-menopausal women was found to be ineffective. Side effects of finasteride include lack of libido, lack of potency, and mild reduction in semen. Because of potential severe teratogenic problems for male fetuses, the drug is contraindicated for use by pre-menopausal women.
Additional drugs for treating androgenetic alopecia in women include oral contraceptives (e.g., ethinyl estradiol-ethynodiol diacetate, desogesterl-ethynyl estradiol, and ethinyl estradiol-norgesterimate), which can reduce hair loss and sometimes lead to slight hair growth (Whiting, “Disorders of Hair,” In: Scientific American Medicine, ed. by Dale and Federman, New York:Web MD Scientific American Medicine, 1999, pages 2:XIII:1-7). Oral spironlactone and dexamethasone have also found use in treatment of female patients.
For other types of alopecia, various approaches include anthralin, psoralen and ultraviolet A, steroids, topical immunotherapy, immunosuppressives, long-term antimicrobial treatment, etc. However, these treatment regimes present various risks and associated side effects, some of which may be severe. Thus, there remains a need for additional compositions and methods to promote hair growth.